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Mitchell A Watsky, Xiaowen Lu; Effect of Vitamin D Receptor Knockout on Diabetic Mouse Corneal Epithelial Wound Healing. Invest. Ophthalmol. Vis. Sci. 2016;57(12):1254.
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© ARVO (1962-2015); The Authors (2016-present)
Diabetes is a significant complicating factor in numerous pathological conditions, and diabetic keratopathy effects approximately 70% of all diabetics. Our recent studies determined that vitamin D receptor (VDR) knockout adversely affects corneal wound healing. This study was designed to investigate VDR knockout effects on corneal epithelial wound healing of diabetic mice.
The low dose streptozotocin injection method was used to induce diabetes mellitus in VDR heterozygous (HET) and VDR knockout (KO) mice along with their wildtype (WT) littermates. Corneal epithelium wound healing experiments were carried out in these mice. Mice were anesthetized and 2 mm central wounds were made using an Alger brush. Wound closure was measured at 0, 12, 20, 28, 36, 48, 60, and 72 h after wounding (measurements stopped if the wound was completely healed) by photographing fluorescein-stained corneas and digitally outlining the wound margins and calculating the wound areas using Olympus CellSens Dimension software. Mice were anesthetized with isoflurane administered through an anesthesia vaporizer for cornea photography.
Wound areas versus time were plotted and a linear regression was run on the data. Healing rates were equated to the regression slope. A rate of -0.018 mm/h was measured in 6-week diabetic duration KO mice versus a rate of -0.05 mm/h in 6-week WT diabetic mice. A rate of -0.021 mm/h was measured in 8-week duration diabetic KO mice versus a rate of -0.046 mm/h in 8-week WT diabetic mice. KO diabetic mice of 6- and 8-week diabetes duration had significantly slower healing rates than WT diabetic mice. There was no significant difference in the healing rate of 4-week diabetic KO mice versus 4-week diabetic WT mice.
KO diabetic mice have significantly slower healing rates than the WT diabetic mice of 6- and 8-week diabetes duration. Vitamin D appears to exert a significant influence early in the development of diabetic keratopathy.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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